Identification of novel functional brain proteins for treatment-resistant schizophrenia: Based on a proteome-wide association study

Abstract Objective Genetic approaches are increasingly advantageous in characterizing treatment-resistant schizophrenia (TRS). We aimed to identify TRS-associated functional brain proteins, providing a potential pathway for improving psychiatric classification and developing better-tailored therape...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Wenming Wei [verfasserIn] Huijie Zhang [verfasserIn] Bolun Cheng [verfasserIn] Xiaoyue Qin [verfasserIn] Dan He [verfasserIn] Na Zhang [verfasserIn] Yijing Zhao [verfasserIn] Qingqing Cai [verfasserIn] Sirong Shi [verfasserIn] Xiaoge Chu [verfasserIn] Yan Wen [verfasserIn] Huan Liu [verfasserIn] Yumeng Jia [verfasserIn] Feng Zhang [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Human brain proteins inflammation lipid oxidation mitochondria proteome-wide association study treatment-resistant schizophrenia

Übergeordnetes Werk:	In: European Psychiatry - Cambridge University Press, 2020, 66(2023)
Übergeordnetes Werk:	volume:66 ; year:2023

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.1192/j.eurpsy.2023.20

Katalog-ID:	DOAJ089306244

Internformat


LEADER	01000caa a22002652 4500
001	DOAJ089306244
003	DE-627
005	20230526105017.0
007	cr uuu---uuuuu
008	230505s2023 xx \|\|\|\|\|o 00\| \|\|eng c
024	7		\|a 10.1192/j.eurpsy.2023.20 \|2 doi
035			\|a (DE-627)DOAJ089306244
035			\|a (DE-599)DOAJ472fff5341a34b8fadb2e11132003517
040			\|a DE-627 \|b ger \|c DE-627 \|e rakwb
041			\|a eng
050		0	\|a RC435-571
100	0		\|a Wenming Wei \|e verfasserin \|4 aut
245	1	0	\|a Identification of novel functional brain proteins for treatment-resistant schizophrenia: Based on a proteome-wide association study
264		1	\|c 2023
336			\|a Text \|b txt \|2 rdacontent
337			\|a Computermedien \|b c \|2 rdamedia
338			\|a Online-Ressource \|b cr \|2 rdacarrier
520			\|a Abstract Objective Genetic approaches are increasingly advantageous in characterizing treatment-resistant schizophrenia (TRS). We aimed to identify TRS-associated functional brain proteins, providing a potential pathway for improving psychiatric classification and developing better-tailored therapeutic targets. Methods TRS-related proteome-wide association studies (PWAS) were conducted on genome-wide association studies (GWAS) from CLOZUK and the Psychiatric Genomics Consortium (PGC), which provided TRS individuals (n = 10,501) and non-TRS individuals (n = 20,325), respectively. The reference datasets for the human brain proteome were obtained from ROS/MAP and Banner, with 8,356 and 11,518 proteins collected, respectively. We then performed colocalization analysis and functional enrichment analysis to further explore the biological functions of the proteins identified by PWAS. Results In PWAS, two statistically significant proteins were identified using the ROS/MAP and then replicated using the Banner reference dataset, including CPT2 (P PWAS-ROS/MAP = 4.15 × 10−2 and P PWAS-Banner = 3.38 × 10−3) and APOL2 (P PWAS-ROS/MAP = 4.49 × 10−3 and P PWAS-Banner = 8.26 × 10−3). Colocalization analysis identified three variants that were causally related to protein expression in the human brain, including CCDC91 (PP4 = 0.981), PRDX1 (PP4 = 0.894), and WARS2 (PP4 = 0.757). We extended PWAS results from gene-based analysis to pathway-based analysis, identifying 14 gene ontology (GO) terms and the only candidate pathway for TRS, metabolic pathways (all P < 0.05). Conclusions Our results identified two protein biomarkers, and cautiously support that the pathological mechanism of TRS is linked to lipid oxidation and inflammation, where mitochondria-related functions may play a role.
650		4	\|a Human brain proteins
650		4	\|a inflammation
650		4	\|a lipid oxidation
650		4	\|a mitochondria
650		4	\|a proteome-wide association study
650		4	\|a treatment-resistant schizophrenia
653		0	\|a Psychiatry
700	0		\|a Huijie Zhang \|e verfasserin \|4 aut
700	0		\|a Bolun Cheng \|e verfasserin \|4 aut
700	0		\|a Xiaoyue Qin \|e verfasserin \|4 aut
700	0		\|a Dan He \|e verfasserin \|4 aut
700	0		\|a Na Zhang \|e verfasserin \|4 aut
700	0		\|a Yijing Zhao \|e verfasserin \|4 aut
700	0		\|a Qingqing Cai \|e verfasserin \|4 aut
700	0		\|a Sirong Shi \|e verfasserin \|4 aut
700	0		\|a Xiaoge Chu \|e verfasserin \|4 aut
700	0		\|a Yan Wen \|e verfasserin \|4 aut
700	0		\|a Huan Liu \|e verfasserin \|4 aut
700	0		\|a Yumeng Jia \|e verfasserin \|4 aut
700	0		\|a Feng Zhang \|e verfasserin \|4 aut
773	0	8	\|i In \|t European Psychiatry \|d Cambridge University Press, 2020 \|g 66(2023) \|w (DE-627)320445070 \|w (DE-600)2005377-0 \|x 17783585 \|7 nnns
773	1	8	\|g volume:66 \|g year:2023
856	4	0	\|u https://doi.org/10.1192/j.eurpsy.2023.20 \|z kostenfrei
856	4	0	\|u https://doaj.org/article/472fff5341a34b8fadb2e11132003517 \|z kostenfrei
856	4	0	\|u https://www.cambridge.org/core/product/identifier/S0924933823000202/type/journal_article \|z kostenfrei
856	4	2	\|u https://doaj.org/toc/0924-9338 \|y Journal toc \|z kostenfrei
856	4	2	\|u https://doaj.org/toc/1778-3585 \|y Journal toc \|z kostenfrei
912			\|a GBV_USEFLAG_A
912			\|a SYSFLAG_A
912			\|a GBV_DOAJ
912			\|a GBV_ILN_20
912			\|a GBV_ILN_22
912			\|a GBV_ILN_23
912			\|a GBV_ILN_24
912			\|a GBV_ILN_31
912			\|a GBV_ILN_39
912			\|a GBV_ILN_40
912			\|a GBV_ILN_60
912			\|a GBV_ILN_62
912			\|a GBV_ILN_63
912			\|a GBV_ILN_65
912			\|a GBV_ILN_69
912			\|a GBV_ILN_73
912			\|a GBV_ILN_74
912			\|a GBV_ILN_95
912			\|a GBV_ILN_105
912			\|a GBV_ILN_110
912			\|a GBV_ILN_151
912			\|a GBV_ILN_161
912			\|a GBV_ILN_170
912			\|a GBV_ILN_206
912			\|a GBV_ILN_213
912			\|a GBV_ILN_217
912			\|a GBV_ILN_230
912			\|a GBV_ILN_285
912			\|a GBV_ILN_293
912			\|a GBV_ILN_374
912			\|a GBV_ILN_602
912			\|a GBV_ILN_636
912			\|a GBV_ILN_2004
912			\|a GBV_ILN_2014
912			\|a GBV_ILN_2110
912			\|a GBV_ILN_2336
912			\|a GBV_ILN_2470
912			\|a GBV_ILN_4012
912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4112
912			\|a GBV_ILN_4125
912			\|a GBV_ILN_4126
912			\|a GBV_ILN_4249
912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4306
912			\|a GBV_ILN_4307
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4322
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4367
912			\|a GBV_ILN_4700
951			\|a AR
952			\|d 66 \|j 2023

Indexfelder

author_variant	w w ww h z hz b c bc x q xq d h dh n z nz y z yz q c qc s s ss x c xc y w yw h l hl y j yj f z fz
matchkey_str	article:17783585:2023----::dniiainfoefntoabanrtisoteteteitnshzprnaaeo
hierarchy_sort_str	2023
callnumber-subject-code	RC
publishDate	2023
allfields	10.1192/j.eurpsy.2023.20 doi (DE-627)DOAJ089306244 (DE-599)DOAJ472fff5341a34b8fadb2e11132003517 DE-627 ger DE-627 rakwb eng RC435-571 Wenming Wei verfasserin aut Identification of novel functional brain proteins for treatment-resistant schizophrenia: Based on a proteome-wide association study 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Objective Genetic approaches are increasingly advantageous in characterizing treatment-resistant schizophrenia (TRS). We aimed to identify TRS-associated functional brain proteins, providing a potential pathway for improving psychiatric classification and developing better-tailored therapeutic targets. Methods TRS-related proteome-wide association studies (PWAS) were conducted on genome-wide association studies (GWAS) from CLOZUK and the Psychiatric Genomics Consortium (PGC), which provided TRS individuals (n = 10,501) and non-TRS individuals (n = 20,325), respectively. The reference datasets for the human brain proteome were obtained from ROS/MAP and Banner, with 8,356 and 11,518 proteins collected, respectively. We then performed colocalization analysis and functional enrichment analysis to further explore the biological functions of the proteins identified by PWAS. Results In PWAS, two statistically significant proteins were identified using the ROS/MAP and then replicated using the Banner reference dataset, including CPT2 (P PWAS-ROS/MAP = 4.15 × 10−2 and P PWAS-Banner = 3.38 × 10−3) and APOL2 (P PWAS-ROS/MAP = 4.49 × 10−3 and P PWAS-Banner = 8.26 × 10−3). Colocalization analysis identified three variants that were causally related to protein expression in the human brain, including CCDC91 (PP4 = 0.981), PRDX1 (PP4 = 0.894), and WARS2 (PP4 = 0.757). We extended PWAS results from gene-based analysis to pathway-based analysis, identifying 14 gene ontology (GO) terms and the only candidate pathway for TRS, metabolic pathways (all P < 0.05). Conclusions Our results identified two protein biomarkers, and cautiously support that the pathological mechanism of TRS is linked to lipid oxidation and inflammation, where mitochondria-related functions may play a role. Human brain proteins inflammation lipid oxidation mitochondria proteome-wide association study treatment-resistant schizophrenia Psychiatry Huijie Zhang verfasserin aut Bolun Cheng verfasserin aut Xiaoyue Qin verfasserin aut Dan He verfasserin aut Na Zhang verfasserin aut Yijing Zhao verfasserin aut Qingqing Cai verfasserin aut Sirong Shi verfasserin aut Xiaoge Chu verfasserin aut Yan Wen verfasserin aut Huan Liu verfasserin aut Yumeng Jia verfasserin aut Feng Zhang verfasserin aut In European Psychiatry Cambridge University Press, 2020 66(2023) (DE-627)320445070 (DE-600)2005377-0 17783585 nnns volume:66 year:2023 https://doi.org/10.1192/j.eurpsy.2023.20 kostenfrei https://doaj.org/article/472fff5341a34b8fadb2e11132003517 kostenfrei https://www.cambridge.org/core/product/identifier/S0924933823000202/type/journal_article kostenfrei https://doaj.org/toc/0924-9338 Journal toc kostenfrei https://doaj.org/toc/1778-3585 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_217 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2014 GBV_ILN_2110 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 66 2023
spelling	10.1192/j.eurpsy.2023.20 doi (DE-627)DOAJ089306244 (DE-599)DOAJ472fff5341a34b8fadb2e11132003517 DE-627 ger DE-627 rakwb eng RC435-571 Wenming Wei verfasserin aut Identification of novel functional brain proteins for treatment-resistant schizophrenia: Based on a proteome-wide association study 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Objective Genetic approaches are increasingly advantageous in characterizing treatment-resistant schizophrenia (TRS). We aimed to identify TRS-associated functional brain proteins, providing a potential pathway for improving psychiatric classification and developing better-tailored therapeutic targets. Methods TRS-related proteome-wide association studies (PWAS) were conducted on genome-wide association studies (GWAS) from CLOZUK and the Psychiatric Genomics Consortium (PGC), which provided TRS individuals (n = 10,501) and non-TRS individuals (n = 20,325), respectively. The reference datasets for the human brain proteome were obtained from ROS/MAP and Banner, with 8,356 and 11,518 proteins collected, respectively. We then performed colocalization analysis and functional enrichment analysis to further explore the biological functions of the proteins identified by PWAS. Results In PWAS, two statistically significant proteins were identified using the ROS/MAP and then replicated using the Banner reference dataset, including CPT2 (P PWAS-ROS/MAP = 4.15 × 10−2 and P PWAS-Banner = 3.38 × 10−3) and APOL2 (P PWAS-ROS/MAP = 4.49 × 10−3 and P PWAS-Banner = 8.26 × 10−3). Colocalization analysis identified three variants that were causally related to protein expression in the human brain, including CCDC91 (PP4 = 0.981), PRDX1 (PP4 = 0.894), and WARS2 (PP4 = 0.757). We extended PWAS results from gene-based analysis to pathway-based analysis, identifying 14 gene ontology (GO) terms and the only candidate pathway for TRS, metabolic pathways (all P < 0.05). Conclusions Our results identified two protein biomarkers, and cautiously support that the pathological mechanism of TRS is linked to lipid oxidation and inflammation, where mitochondria-related functions may play a role. Human brain proteins inflammation lipid oxidation mitochondria proteome-wide association study treatment-resistant schizophrenia Psychiatry Huijie Zhang verfasserin aut Bolun Cheng verfasserin aut Xiaoyue Qin verfasserin aut Dan He verfasserin aut Na Zhang verfasserin aut Yijing Zhao verfasserin aut Qingqing Cai verfasserin aut Sirong Shi verfasserin aut Xiaoge Chu verfasserin aut Yan Wen verfasserin aut Huan Liu verfasserin aut Yumeng Jia verfasserin aut Feng Zhang verfasserin aut In European Psychiatry Cambridge University Press, 2020 66(2023) (DE-627)320445070 (DE-600)2005377-0 17783585 nnns volume:66 year:2023 https://doi.org/10.1192/j.eurpsy.2023.20 kostenfrei https://doaj.org/article/472fff5341a34b8fadb2e11132003517 kostenfrei https://www.cambridge.org/core/product/identifier/S0924933823000202/type/journal_article kostenfrei https://doaj.org/toc/0924-9338 Journal toc kostenfrei https://doaj.org/toc/1778-3585 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_217 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2014 GBV_ILN_2110 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 66 2023
allfields_unstemmed	10.1192/j.eurpsy.2023.20 doi (DE-627)DOAJ089306244 (DE-599)DOAJ472fff5341a34b8fadb2e11132003517 DE-627 ger DE-627 rakwb eng RC435-571 Wenming Wei verfasserin aut Identification of novel functional brain proteins for treatment-resistant schizophrenia: Based on a proteome-wide association study 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Objective Genetic approaches are increasingly advantageous in characterizing treatment-resistant schizophrenia (TRS). We aimed to identify TRS-associated functional brain proteins, providing a potential pathway for improving psychiatric classification and developing better-tailored therapeutic targets. Methods TRS-related proteome-wide association studies (PWAS) were conducted on genome-wide association studies (GWAS) from CLOZUK and the Psychiatric Genomics Consortium (PGC), which provided TRS individuals (n = 10,501) and non-TRS individuals (n = 20,325), respectively. The reference datasets for the human brain proteome were obtained from ROS/MAP and Banner, with 8,356 and 11,518 proteins collected, respectively. We then performed colocalization analysis and functional enrichment analysis to further explore the biological functions of the proteins identified by PWAS. Results In PWAS, two statistically significant proteins were identified using the ROS/MAP and then replicated using the Banner reference dataset, including CPT2 (P PWAS-ROS/MAP = 4.15 × 10−2 and P PWAS-Banner = 3.38 × 10−3) and APOL2 (P PWAS-ROS/MAP = 4.49 × 10−3 and P PWAS-Banner = 8.26 × 10−3). Colocalization analysis identified three variants that were causally related to protein expression in the human brain, including CCDC91 (PP4 = 0.981), PRDX1 (PP4 = 0.894), and WARS2 (PP4 = 0.757). We extended PWAS results from gene-based analysis to pathway-based analysis, identifying 14 gene ontology (GO) terms and the only candidate pathway for TRS, metabolic pathways (all P < 0.05). Conclusions Our results identified two protein biomarkers, and cautiously support that the pathological mechanism of TRS is linked to lipid oxidation and inflammation, where mitochondria-related functions may play a role. Human brain proteins inflammation lipid oxidation mitochondria proteome-wide association study treatment-resistant schizophrenia Psychiatry Huijie Zhang verfasserin aut Bolun Cheng verfasserin aut Xiaoyue Qin verfasserin aut Dan He verfasserin aut Na Zhang verfasserin aut Yijing Zhao verfasserin aut Qingqing Cai verfasserin aut Sirong Shi verfasserin aut Xiaoge Chu verfasserin aut Yan Wen verfasserin aut Huan Liu verfasserin aut Yumeng Jia verfasserin aut Feng Zhang verfasserin aut In European Psychiatry Cambridge University Press, 2020 66(2023) (DE-627)320445070 (DE-600)2005377-0 17783585 nnns volume:66 year:2023 https://doi.org/10.1192/j.eurpsy.2023.20 kostenfrei https://doaj.org/article/472fff5341a34b8fadb2e11132003517 kostenfrei https://www.cambridge.org/core/product/identifier/S0924933823000202/type/journal_article kostenfrei https://doaj.org/toc/0924-9338 Journal toc kostenfrei https://doaj.org/toc/1778-3585 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_217 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2014 GBV_ILN_2110 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 66 2023
allfieldsGer	10.1192/j.eurpsy.2023.20 doi (DE-627)DOAJ089306244 (DE-599)DOAJ472fff5341a34b8fadb2e11132003517 DE-627 ger DE-627 rakwb eng RC435-571 Wenming Wei verfasserin aut Identification of novel functional brain proteins for treatment-resistant schizophrenia: Based on a proteome-wide association study 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Objective Genetic approaches are increasingly advantageous in characterizing treatment-resistant schizophrenia (TRS). We aimed to identify TRS-associated functional brain proteins, providing a potential pathway for improving psychiatric classification and developing better-tailored therapeutic targets. Methods TRS-related proteome-wide association studies (PWAS) were conducted on genome-wide association studies (GWAS) from CLOZUK and the Psychiatric Genomics Consortium (PGC), which provided TRS individuals (n = 10,501) and non-TRS individuals (n = 20,325), respectively. The reference datasets for the human brain proteome were obtained from ROS/MAP and Banner, with 8,356 and 11,518 proteins collected, respectively. We then performed colocalization analysis and functional enrichment analysis to further explore the biological functions of the proteins identified by PWAS. Results In PWAS, two statistically significant proteins were identified using the ROS/MAP and then replicated using the Banner reference dataset, including CPT2 (P PWAS-ROS/MAP = 4.15 × 10−2 and P PWAS-Banner = 3.38 × 10−3) and APOL2 (P PWAS-ROS/MAP = 4.49 × 10−3 and P PWAS-Banner = 8.26 × 10−3). Colocalization analysis identified three variants that were causally related to protein expression in the human brain, including CCDC91 (PP4 = 0.981), PRDX1 (PP4 = 0.894), and WARS2 (PP4 = 0.757). We extended PWAS results from gene-based analysis to pathway-based analysis, identifying 14 gene ontology (GO) terms and the only candidate pathway for TRS, metabolic pathways (all P < 0.05). Conclusions Our results identified two protein biomarkers, and cautiously support that the pathological mechanism of TRS is linked to lipid oxidation and inflammation, where mitochondria-related functions may play a role. Human brain proteins inflammation lipid oxidation mitochondria proteome-wide association study treatment-resistant schizophrenia Psychiatry Huijie Zhang verfasserin aut Bolun Cheng verfasserin aut Xiaoyue Qin verfasserin aut Dan He verfasserin aut Na Zhang verfasserin aut Yijing Zhao verfasserin aut Qingqing Cai verfasserin aut Sirong Shi verfasserin aut Xiaoge Chu verfasserin aut Yan Wen verfasserin aut Huan Liu verfasserin aut Yumeng Jia verfasserin aut Feng Zhang verfasserin aut In European Psychiatry Cambridge University Press, 2020 66(2023) (DE-627)320445070 (DE-600)2005377-0 17783585 nnns volume:66 year:2023 https://doi.org/10.1192/j.eurpsy.2023.20 kostenfrei https://doaj.org/article/472fff5341a34b8fadb2e11132003517 kostenfrei https://www.cambridge.org/core/product/identifier/S0924933823000202/type/journal_article kostenfrei https://doaj.org/toc/0924-9338 Journal toc kostenfrei https://doaj.org/toc/1778-3585 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_217 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2014 GBV_ILN_2110 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 66 2023
allfieldsSound	10.1192/j.eurpsy.2023.20 doi (DE-627)DOAJ089306244 (DE-599)DOAJ472fff5341a34b8fadb2e11132003517 DE-627 ger DE-627 rakwb eng RC435-571 Wenming Wei verfasserin aut Identification of novel functional brain proteins for treatment-resistant schizophrenia: Based on a proteome-wide association study 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Objective Genetic approaches are increasingly advantageous in characterizing treatment-resistant schizophrenia (TRS). We aimed to identify TRS-associated functional brain proteins, providing a potential pathway for improving psychiatric classification and developing better-tailored therapeutic targets. Methods TRS-related proteome-wide association studies (PWAS) were conducted on genome-wide association studies (GWAS) from CLOZUK and the Psychiatric Genomics Consortium (PGC), which provided TRS individuals (n = 10,501) and non-TRS individuals (n = 20,325), respectively. The reference datasets for the human brain proteome were obtained from ROS/MAP and Banner, with 8,356 and 11,518 proteins collected, respectively. We then performed colocalization analysis and functional enrichment analysis to further explore the biological functions of the proteins identified by PWAS. Results In PWAS, two statistically significant proteins were identified using the ROS/MAP and then replicated using the Banner reference dataset, including CPT2 (P PWAS-ROS/MAP = 4.15 × 10−2 and P PWAS-Banner = 3.38 × 10−3) and APOL2 (P PWAS-ROS/MAP = 4.49 × 10−3 and P PWAS-Banner = 8.26 × 10−3). Colocalization analysis identified three variants that were causally related to protein expression in the human brain, including CCDC91 (PP4 = 0.981), PRDX1 (PP4 = 0.894), and WARS2 (PP4 = 0.757). We extended PWAS results from gene-based analysis to pathway-based analysis, identifying 14 gene ontology (GO) terms and the only candidate pathway for TRS, metabolic pathways (all P < 0.05). Conclusions Our results identified two protein biomarkers, and cautiously support that the pathological mechanism of TRS is linked to lipid oxidation and inflammation, where mitochondria-related functions may play a role. Human brain proteins inflammation lipid oxidation mitochondria proteome-wide association study treatment-resistant schizophrenia Psychiatry Huijie Zhang verfasserin aut Bolun Cheng verfasserin aut Xiaoyue Qin verfasserin aut Dan He verfasserin aut Na Zhang verfasserin aut Yijing Zhao verfasserin aut Qingqing Cai verfasserin aut Sirong Shi verfasserin aut Xiaoge Chu verfasserin aut Yan Wen verfasserin aut Huan Liu verfasserin aut Yumeng Jia verfasserin aut Feng Zhang verfasserin aut In European Psychiatry Cambridge University Press, 2020 66(2023) (DE-627)320445070 (DE-600)2005377-0 17783585 nnns volume:66 year:2023 https://doi.org/10.1192/j.eurpsy.2023.20 kostenfrei https://doaj.org/article/472fff5341a34b8fadb2e11132003517 kostenfrei https://www.cambridge.org/core/product/identifier/S0924933823000202/type/journal_article kostenfrei https://doaj.org/toc/0924-9338 Journal toc kostenfrei https://doaj.org/toc/1778-3585 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_217 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2014 GBV_ILN_2110 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 66 2023
language	English
source	In European Psychiatry 66(2023) volume:66 year:2023
sourceStr	In European Psychiatry 66(2023) volume:66 year:2023
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Human brain proteins inflammation lipid oxidation mitochondria proteome-wide association study treatment-resistant schizophrenia Psychiatry
isfreeaccess_bool	true
container_title	European Psychiatry
authorswithroles_txt_mv	Wenming Wei @@aut@@ Huijie Zhang @@aut@@ Bolun Cheng @@aut@@ Xiaoyue Qin @@aut@@ Dan He @@aut@@ Na Zhang @@aut@@ Yijing Zhao @@aut@@ Qingqing Cai @@aut@@ Sirong Shi @@aut@@ Xiaoge Chu @@aut@@ Yan Wen @@aut@@ Huan Liu @@aut@@ Yumeng Jia @@aut@@ Feng Zhang @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	320445070
id	DOAJ089306244
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ089306244</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230526105017.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230505s2023 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1192/j.eurpsy.2023.20</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ089306244</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ472fff5341a34b8fadb2e11132003517</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC435-571</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Wenming Wei</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Identification of novel functional brain proteins for treatment-resistant schizophrenia: Based on a proteome-wide association study</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2023</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Objective Genetic approaches are increasingly advantageous in characterizing treatment-resistant schizophrenia (TRS). We aimed to identify TRS-associated functional brain proteins, providing a potential pathway for improving psychiatric classification and developing better-tailored therapeutic targets. Methods TRS-related proteome-wide association studies (PWAS) were conducted on genome-wide association studies (GWAS) from CLOZUK and the Psychiatric Genomics Consortium (PGC), which provided TRS individuals (n = 10,501) and non-TRS individuals (n = 20,325), respectively. The reference datasets for the human brain proteome were obtained from ROS/MAP and Banner, with 8,356 and 11,518 proteins collected, respectively. We then performed colocalization analysis and functional enrichment analysis to further explore the biological functions of the proteins identified by PWAS. Results In PWAS, two statistically significant proteins were identified using the ROS/MAP and then replicated using the Banner reference dataset, including CPT2 (P PWAS-ROS/MAP = 4.15 × 10−2 and P PWAS-Banner = 3.38 × 10−3) and APOL2 (P PWAS-ROS/MAP = 4.49 × 10−3 and P PWAS-Banner = 8.26 × 10−3). Colocalization analysis identified three variants that were causally related to protein expression in the human brain, including CCDC91 (PP4 = 0.981), PRDX1 (PP4 = 0.894), and WARS2 (PP4 = 0.757). We extended PWAS results from gene-based analysis to pathway-based analysis, identifying 14 gene ontology (GO) terms and the only candidate pathway for TRS, metabolic pathways (all P < 0.05). Conclusions Our results identified two protein biomarkers, and cautiously support that the pathological mechanism of TRS is linked to lipid oxidation and inflammation, where mitochondria-related functions may play a role.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Human brain proteins</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">inflammation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">lipid oxidation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">mitochondria</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">proteome-wide association study</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">treatment-resistant schizophrenia</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Psychiatry</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Huijie Zhang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Bolun Cheng</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Xiaoyue Qin</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Dan He</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Na Zhang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yijing Zhao</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Qingqing Cai</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sirong Shi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Xiaoge Chu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yan Wen</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Huan Liu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yumeng Jia</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Feng Zhang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">European Psychiatry</subfield><subfield code="d">Cambridge University Press, 2020</subfield><subfield code="g">66(2023)</subfield><subfield code="w">(DE-627)320445070</subfield><subfield code="w">(DE-600)2005377-0</subfield><subfield code="x">17783585</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:66</subfield><subfield code="g">year:2023</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1192/j.eurpsy.2023.20</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/472fff5341a34b8fadb2e11132003517</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://www.cambridge.org/core/product/identifier/S0924933823000202/type/journal_article</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/0924-9338</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/1778-3585</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_217</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_374</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_636</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2004</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2336</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2470</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">66</subfield><subfield code="j">2023</subfield></datafield></record></collection>
callnumber-first	R - Medicine
author	Wenming Wei
spellingShingle	Wenming Wei misc RC435-571 misc Human brain proteins misc inflammation misc lipid oxidation misc mitochondria misc proteome-wide association study misc treatment-resistant schizophrenia misc Psychiatry Identification of novel functional brain proteins for treatment-resistant schizophrenia: Based on a proteome-wide association study
authorStr	Wenming Wei
ppnlink_with_tag_str_mv	@@773@@(DE-627)320445070
format	electronic Article
delete_txt_mv	keep
author_role	aut aut aut aut aut aut aut aut aut aut aut aut aut aut
collection	DOAJ
remote_str	true
callnumber-label	RC435-571
illustrated	Not Illustrated
issn	17783585
topic_title	RC435-571 Identification of novel functional brain proteins for treatment-resistant schizophrenia: Based on a proteome-wide association study Human brain proteins inflammation lipid oxidation mitochondria proteome-wide association study treatment-resistant schizophrenia
topic	misc RC435-571 misc Human brain proteins misc inflammation misc lipid oxidation misc mitochondria misc proteome-wide association study misc treatment-resistant schizophrenia misc Psychiatry
topic_unstemmed	misc RC435-571 misc Human brain proteins misc inflammation misc lipid oxidation misc mitochondria misc proteome-wide association study misc treatment-resistant schizophrenia misc Psychiatry
topic_browse	misc RC435-571 misc Human brain proteins misc inflammation misc lipid oxidation misc mitochondria misc proteome-wide association study misc treatment-resistant schizophrenia misc Psychiatry
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
format_main_str_mv	Text Zeitschrift/Artikel
carriertype_str_mv	cr
hierarchy_parent_title	European Psychiatry
hierarchy_parent_id	320445070
hierarchy_top_title	European Psychiatry
isfreeaccess_txt	true
familylinks_str_mv	(DE-627)320445070 (DE-600)2005377-0
title	Identification of novel functional brain proteins for treatment-resistant schizophrenia: Based on a proteome-wide association study
ctrlnum	(DE-627)DOAJ089306244 (DE-599)DOAJ472fff5341a34b8fadb2e11132003517
title_full	Identification of novel functional brain proteins for treatment-resistant schizophrenia: Based on a proteome-wide association study
author_sort	Wenming Wei
journal	European Psychiatry
journalStr	European Psychiatry
callnumber-first-code	R
lang_code	eng
isOA_bool	true
recordtype	marc
publishDateSort	2023
contenttype_str_mv	txt
author_browse	Wenming Wei Huijie Zhang Bolun Cheng Xiaoyue Qin Dan He Na Zhang Yijing Zhao Qingqing Cai Sirong Shi Xiaoge Chu Yan Wen Huan Liu Yumeng Jia Feng Zhang
container_volume	66
class	RC435-571
format_se	Elektronische Aufsätze
author-letter	Wenming Wei
doi_str_mv	10.1192/j.eurpsy.2023.20
author2-role	verfasserin
title_sort	identification of novel functional brain proteins for treatment-resistant schizophrenia: based on a proteome-wide association study
callnumber	RC435-571
title_auth	Identification of novel functional brain proteins for treatment-resistant schizophrenia: Based on a proteome-wide association study
abstract	Abstract Objective Genetic approaches are increasingly advantageous in characterizing treatment-resistant schizophrenia (TRS). We aimed to identify TRS-associated functional brain proteins, providing a potential pathway for improving psychiatric classification and developing better-tailored therapeutic targets. Methods TRS-related proteome-wide association studies (PWAS) were conducted on genome-wide association studies (GWAS) from CLOZUK and the Psychiatric Genomics Consortium (PGC), which provided TRS individuals (n = 10,501) and non-TRS individuals (n = 20,325), respectively. The reference datasets for the human brain proteome were obtained from ROS/MAP and Banner, with 8,356 and 11,518 proteins collected, respectively. We then performed colocalization analysis and functional enrichment analysis to further explore the biological functions of the proteins identified by PWAS. Results In PWAS, two statistically significant proteins were identified using the ROS/MAP and then replicated using the Banner reference dataset, including CPT2 (P PWAS-ROS/MAP = 4.15 × 10−2 and P PWAS-Banner = 3.38 × 10−3) and APOL2 (P PWAS-ROS/MAP = 4.49 × 10−3 and P PWAS-Banner = 8.26 × 10−3). Colocalization analysis identified three variants that were causally related to protein expression in the human brain, including CCDC91 (PP4 = 0.981), PRDX1 (PP4 = 0.894), and WARS2 (PP4 = 0.757). We extended PWAS results from gene-based analysis to pathway-based analysis, identifying 14 gene ontology (GO) terms and the only candidate pathway for TRS, metabolic pathways (all P < 0.05). Conclusions Our results identified two protein biomarkers, and cautiously support that the pathological mechanism of TRS is linked to lipid oxidation and inflammation, where mitochondria-related functions may play a role.
abstractGer	Abstract Objective Genetic approaches are increasingly advantageous in characterizing treatment-resistant schizophrenia (TRS). We aimed to identify TRS-associated functional brain proteins, providing a potential pathway for improving psychiatric classification and developing better-tailored therapeutic targets. Methods TRS-related proteome-wide association studies (PWAS) were conducted on genome-wide association studies (GWAS) from CLOZUK and the Psychiatric Genomics Consortium (PGC), which provided TRS individuals (n = 10,501) and non-TRS individuals (n = 20,325), respectively. The reference datasets for the human brain proteome were obtained from ROS/MAP and Banner, with 8,356 and 11,518 proteins collected, respectively. We then performed colocalization analysis and functional enrichment analysis to further explore the biological functions of the proteins identified by PWAS. Results In PWAS, two statistically significant proteins were identified using the ROS/MAP and then replicated using the Banner reference dataset, including CPT2 (P PWAS-ROS/MAP = 4.15 × 10−2 and P PWAS-Banner = 3.38 × 10−3) and APOL2 (P PWAS-ROS/MAP = 4.49 × 10−3 and P PWAS-Banner = 8.26 × 10−3). Colocalization analysis identified three variants that were causally related to protein expression in the human brain, including CCDC91 (PP4 = 0.981), PRDX1 (PP4 = 0.894), and WARS2 (PP4 = 0.757). We extended PWAS results from gene-based analysis to pathway-based analysis, identifying 14 gene ontology (GO) terms and the only candidate pathway for TRS, metabolic pathways (all P < 0.05). Conclusions Our results identified two protein biomarkers, and cautiously support that the pathological mechanism of TRS is linked to lipid oxidation and inflammation, where mitochondria-related functions may play a role.
abstract_unstemmed	Abstract Objective Genetic approaches are increasingly advantageous in characterizing treatment-resistant schizophrenia (TRS). We aimed to identify TRS-associated functional brain proteins, providing a potential pathway for improving psychiatric classification and developing better-tailored therapeutic targets. Methods TRS-related proteome-wide association studies (PWAS) were conducted on genome-wide association studies (GWAS) from CLOZUK and the Psychiatric Genomics Consortium (PGC), which provided TRS individuals (n = 10,501) and non-TRS individuals (n = 20,325), respectively. The reference datasets for the human brain proteome were obtained from ROS/MAP and Banner, with 8,356 and 11,518 proteins collected, respectively. We then performed colocalization analysis and functional enrichment analysis to further explore the biological functions of the proteins identified by PWAS. Results In PWAS, two statistically significant proteins were identified using the ROS/MAP and then replicated using the Banner reference dataset, including CPT2 (P PWAS-ROS/MAP = 4.15 × 10−2 and P PWAS-Banner = 3.38 × 10−3) and APOL2 (P PWAS-ROS/MAP = 4.49 × 10−3 and P PWAS-Banner = 8.26 × 10−3). Colocalization analysis identified three variants that were causally related to protein expression in the human brain, including CCDC91 (PP4 = 0.981), PRDX1 (PP4 = 0.894), and WARS2 (PP4 = 0.757). We extended PWAS results from gene-based analysis to pathway-based analysis, identifying 14 gene ontology (GO) terms and the only candidate pathway for TRS, metabolic pathways (all P < 0.05). Conclusions Our results identified two protein biomarkers, and cautiously support that the pathological mechanism of TRS is linked to lipid oxidation and inflammation, where mitochondria-related functions may play a role.
collection_details	GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_217 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2014 GBV_ILN_2110 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700
title_short	Identification of novel functional brain proteins for treatment-resistant schizophrenia: Based on a proteome-wide association study
url	https://doi.org/10.1192/j.eurpsy.2023.20 https://doaj.org/article/472fff5341a34b8fadb2e11132003517 https://www.cambridge.org/core/product/identifier/S0924933823000202/type/journal_article https://doaj.org/toc/0924-9338 https://doaj.org/toc/1778-3585
remote_bool	true
author2	Huijie Zhang Bolun Cheng Xiaoyue Qin Dan He Na Zhang Yijing Zhao Qingqing Cai Sirong Shi Xiaoge Chu Yan Wen Huan Liu Yumeng Jia Feng Zhang
author2Str	Huijie Zhang Bolun Cheng Xiaoyue Qin Dan He Na Zhang Yijing Zhao Qingqing Cai Sirong Shi Xiaoge Chu Yan Wen Huan Liu Yumeng Jia Feng Zhang
ppnlink	320445070
callnumber-subject	RC - Internal Medicine
mediatype_str_mv	c
isOA_txt	true
hochschulschrift_bool	false
doi_str	10.1192/j.eurpsy.2023.20
callnumber-a	RC435-571
up_date	2024-07-03T22:23:32.290Z
_version_	1803598338242641920
fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ089306244</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230526105017.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230505s2023 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1192/j.eurpsy.2023.20</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ089306244</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ472fff5341a34b8fadb2e11132003517</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC435-571</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Wenming Wei</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Identification of novel functional brain proteins for treatment-resistant schizophrenia: Based on a proteome-wide association study</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2023</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Objective Genetic approaches are increasingly advantageous in characterizing treatment-resistant schizophrenia (TRS). We aimed to identify TRS-associated functional brain proteins, providing a potential pathway for improving psychiatric classification and developing better-tailored therapeutic targets. Methods TRS-related proteome-wide association studies (PWAS) were conducted on genome-wide association studies (GWAS) from CLOZUK and the Psychiatric Genomics Consortium (PGC), which provided TRS individuals (n = 10,501) and non-TRS individuals (n = 20,325), respectively. The reference datasets for the human brain proteome were obtained from ROS/MAP and Banner, with 8,356 and 11,518 proteins collected, respectively. We then performed colocalization analysis and functional enrichment analysis to further explore the biological functions of the proteins identified by PWAS. Results In PWAS, two statistically significant proteins were identified using the ROS/MAP and then replicated using the Banner reference dataset, including CPT2 (P PWAS-ROS/MAP = 4.15 × 10−2 and P PWAS-Banner = 3.38 × 10−3) and APOL2 (P PWAS-ROS/MAP = 4.49 × 10−3 and P PWAS-Banner = 8.26 × 10−3). Colocalization analysis identified three variants that were causally related to protein expression in the human brain, including CCDC91 (PP4 = 0.981), PRDX1 (PP4 = 0.894), and WARS2 (PP4 = 0.757). We extended PWAS results from gene-based analysis to pathway-based analysis, identifying 14 gene ontology (GO) terms and the only candidate pathway for TRS, metabolic pathways (all P < 0.05). Conclusions Our results identified two protein biomarkers, and cautiously support that the pathological mechanism of TRS is linked to lipid oxidation and inflammation, where mitochondria-related functions may play a role.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Human brain proteins</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">inflammation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">lipid oxidation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">mitochondria</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">proteome-wide association study</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">treatment-resistant schizophrenia</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Psychiatry</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Huijie Zhang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Bolun Cheng</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Xiaoyue Qin</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Dan He</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Na Zhang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yijing Zhao</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Qingqing Cai</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sirong Shi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Xiaoge Chu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yan Wen</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Huan Liu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yumeng Jia</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Feng Zhang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">European Psychiatry</subfield><subfield code="d">Cambridge University Press, 2020</subfield><subfield code="g">66(2023)</subfield><subfield code="w">(DE-627)320445070</subfield><subfield code="w">(DE-600)2005377-0</subfield><subfield code="x">17783585</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:66</subfield><subfield code="g">year:2023</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1192/j.eurpsy.2023.20</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/472fff5341a34b8fadb2e11132003517</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://www.cambridge.org/core/product/identifier/S0924933823000202/type/journal_article</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/0924-9338</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/1778-3585</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_217</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_374</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_636</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2004</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2336</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2470</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">66</subfield><subfield code="j">2023</subfield></datafield></record></collection>
score	7.399453

Nicht das Richtige dabei?

Schreiben Sie uns!

Identification of novel functional brain proteins for treatment-resistant schizophrenia: Based on a proteome-wide association study

Nicht das Richtige dabei?

Zugang & Verfügbarkeit

Vorhandene Bände

Nicht das Richtige dabei?